Halomethylation reactions are well known reactions of aromatic compounds. The predominant halomethylation reactions are chloromethylation and bromomethylation. In recent years chloromethylating reagents have been recognized as highly hazardous reagents. For example bis-chloromethyl ether has been identified as a carcinogen which is ban in many countries in the world. Hence, bromomethylating reagents which have been recognized as less hazardous than the chloro-analogues thereof, offer an alternative halomethylating agent. Furthermore, bromomethylated compounds are more versatile as synthetic intermediates than the chloro-analogues. Olah et al (Synthesis (Communications) (1974), (8), 560–561) describes other halomethylating agents and the application thereof in the halomethylating of substituted aromatic compounds. The advantages of bromomethylating agents in terms of regioselectivity has been demonstrated, for example, by Zavada et al (Synthesis (short papers) (1994) vol. 11, 1132) and Garg et al (Synlett (1998) vol. 3, 310–312). The advantageous reactivity of bromomethylating reagents has been described in U.S. Pat. No. 4,559,392 to Raban and Begtrup et al (Synthesis (1993), 861). Nonetheless, bromomethylating reactions require temperatures ranging from 60° C. and higher, pressure exceedingly higher than atmospheric pressure and long reaction time. The conditions of the reaction increase (e.g. higher temperature, longer reaction time) with the decreasing reactivity of the substrate. Often the selectivity of the reaction is adversely effected by these factors and reaction conditions which may result in the formation of undesirable by-products which lower the yield and complicate the isolation process, which subsequently, have an adverse impact on the economical value of the process.
In view of the aforementioned there is a long felt need for a bromomethylating process which is less hazardous than the analogous chloromethylation and is conducted under moderate conditions, wherein said process is of economical value.
It is therefore an object of the present invention to provide a bromomethylating process which can be applied readily to a wide variety of substrates, including substrates of relatively low reactivity.
It is another object of the present invention to provide a bromomethylating process which requires relatively moderate conditions in terms of temperature, pressure and time.
A further object of the present invention is to provide a bromomethylating process for the preparation of bis-bromomethyl biphenyl.
It is yet another object of the present invention to provide a process which overcomes the disadvantages of the prior art.
Other objects of the invention will become apparent as the description proceeds.